Transfusion needs after CD19 CAR T‐cells for large B‐cell lymphoma: predictive factors and impact on outcome. A DESCAR‐T study.

Introduction: Patients undergoing CAR T-cell therapy may experience severe cytopenias due to lymphodepleting chemotherapy and/or CAR T-cells. Transfusion needs represent a surrogate marker of severe anemia and thrombocytopenia. Transfusion needs may impact patients’ quality of life and CAR T-cells efficacy through transfusion-related immunomodulation. Here, we aimed to describe transfusion needs of patients receiving commercial CD19 CAR T-cells for relapse or refractory large B-cell lymphoma (LBCL), identify predictive factors associated with transfusions and search for correlations with CAR T-cells efficacy. Methods: Clinical data were collected form the DESCAR-T registry, the French national real-life registry for all patients treated with commercial CAR T-cells. Transfusion data were collected from the French national blood bank. We included all LBCL patients with at least 6-months follow-up from CAR T-cell infusion. Patients were censored for transfusions at relapse, new treatment onset, or death. Results: From August 2018 to September 2022, 671 patients in the DESCAR-T registry met the eligibility criteria. Overall, 382 patients (56.9%) received at least one transfusion after CAR T-cell infusion: 53.5% at the early phase (i.e. within the first month), and 37.8% at the late phase (i.e. beyond one month). Only 6% of the patients required transfusions beyond 3 months. The mean number of red blood cells (RBC) units and platelets transfusion per patient after CAR T-cell therapy were 3.5 (range, 0–90) and 5.1 (range, 0–127), respectively. Factors associated with transfusion needs after CAR T-cells therapy are presented in Table 1. Age, international prognostic index, primary refractory status, prior ASCT, bulk disease, and severe cytokine release syndrome (CRS) were associated with early but not late RBC transfusions. Early and late platelets transfusion shared the same risk factors except for severe CRS. No association was found between transfusions and response rate after CAR T-cell therapy. However, early transfusions (RBC and platelets) were associated with a shorter progression-free survival (median PFS = 3.2 vs. 6.0 months, p = 0.0168) and overall survival (median OS = 9.3 vs. 23.6 months, p < .0001). Late platelets transfusions were associated with decreased PFS (median = 5.6 vs. 12.0 months, p = 0.0072) and OS (median = 13.8 vs. NR, p < .0001) whereas late RBC transfusions did not impact PFS nor OS. Conclusion: In our study, 56.9% of patients received transfusions after CAR T-cell therapy. We identified risk factors associated with early and late transfusion needs. Early transfusions (RBC and platelets) and late platelets transfusion were associated with worse survival. Our data shed light on the mechanisms of early and late anemia and thrombocytopenia, and on the potential impact of transfusions on CAR T-cells efficacy. Encore Abstract - previously submitted to EHA 2023 Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies Conflicts of interests pertinent to the abstract. E. Bachy Honoraria: Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics Research funding: Amgen, BMS Other remuneration: Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer G. Cartron Consultant or advisory role: Roche, Celgene-BMS, Onwards Therapeutics, MedxCell, EmerCell, MabQi Honoraria: Sanofi, Abbvie, Takeda, Roche, Janssen, Roche, Celgene, Novartis, Incyte Other remuneration: Consulting fees from from Roche and Celgene-BMS T. Gastinne Consultant or advisory role: Takeda, Gilead Sciences Honoraria: Pfizer, Takeda, Gilead Sciences Educational grants: Roche, Pfizer F. Morschhauser Consultant or advisory role: Novartis and Gilead K. Bouabdallah Consultant or advisory role: Kite/Gilead, Takeda Honoraria: Kite/Gilead, Takeda Educational grants: Kite/Gilead O. Casasnovas Consultant or advisory role: ROCHE, TAKEDA, GLIEAD/KITE, MSD, BMS Honoraria: ROCHE, TAKEDA, GILEAD/KITE, MSD, BMS, AMGEN, ABBVIE, JANSSEN Educational grants: ROCHE, TAKEDA, GILEAD/KITE, MSD, BMS, AMGEN, ABBVIE, JANSSEN Other remuneration: ROCHE, TAKEDA, GILEAD/KITE (research funding to the institution) S. Choquet Other remuneration: Novartis, Kite Gilead C. Castilla-Llorente Honoraria: Gilead/Kite S. Guidez Honoraria: Gilead, Novartis, Incyte, Roche M. Loschi Honoraria: Alexion, BMS Celgene, Gilead, Iqone, MSD, Novartis, Pfizer, Sanofi and Sobi L. Drieu La Rochelle Consultant or advisory role: Gilead/kite Educational grants: TAKEDA, Gilead/kite R. Houot Consultant or advisory role: Kite/Gilead, Novartis, Bristol-Myers Squibb/Celgene, ADC Therapeutics, Incyte, Miltenyi Honoraria: Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda and Roche